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Case Reports
. 2020 Mar 10;56(3):119.
doi: 10.3390/medicina56030119.

Recurrent Germline BRCA2 Gene Mutation in Lithuanian Family

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Free PMC article
Case Reports

Recurrent Germline BRCA2 Gene Mutation in Lithuanian Family

Ieva Sadzevičienė et al. Medicina (Kaunas). .
Free PMC article

Abstract

Approximately 10% of all breast cancer (BC) cases are familial and caused by inheritance of mutant BRCA1, BRCA2, or some other genes from the same DNA reparation pathway. Genetic counseling in families with cancer history is a powerful means for early cancer detection and active risk reduction through preventive interventions. This is the first report of the rare inherited BRCA2 frameshift-deletion mutation c.3847_3848delGT in one Lithuanian pedigree with the intense familial history of BC. Three BRCA2-positive blood relatives with BC of different biological types were identified in this pedigree with the same type mutation. All three cases were diagnosed with advanced stage ductal carcinoma. Markedly, polymorphic cells and numerous mitoses were identified in BC from the cases. Two patients from the family were diagnosed with the triple negative tumors, while one case had early onset of the hormone positive BC. Despite the variation in clinical and biological presentation of BC, all cases showed a good response to conventional treatment. In conclusion, the strong influence of BRCA2 mutation on the onset of BC of various biological types reveals the complexity of genetic counselling in families with BC history.

Keywords: BRCA testing; BRCA2; breast cancer; c.3847_3848delGT.

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Pedigree of individuals with BRCA2 c.3847_3848delGT mutation. Patients described in details are indicated by the arrow. Three sisters were diagnosed with breast cancer, while genetic testing was performed for two of them. Two daughters of the proband were tested for BRCA2 mutation, and one was mutation and cancer-positive. Y.o.: Age at diagnosis is indicated.
Figure 2
Figure 2
Histology specimens of the proband (age 62) (A,D), younger sister, Patient 2 (age 32) right breast tumor, year 2008 (B,E) and left breast lesion in 2014 (C,F). Proband’s tumor Hematoxylin and Eosin (HE) slides demonstrate poorly differentiated (G3, Nottingham grade 8) ductal carcinoma composed of confluent trabecular structures and tumor sheets without any presence of glandular differentiation (A). Tumor cells reveal marked nuclear polymorphism (D) and a high mitotic rate (up to 10 mitoses per 10 high-power fields (HPF)). Patient 2′s (year 2008) right breast tumor was diagnosed as high grade ductal carcinoma with solid growth pattern (B) and highly polymorphic tumor cells and numerous mitoses (E). The tumor was triple negative, expressed high-molecular-weight cytokeratins (CK5 in particular), and was regarded as “basal-like carcinoma”. Note the pushing margin in the periphery of the tumor (B). Patient 2′s left breast lesion (year 2014) with ductal carcinoma in situ (DCIS) of high grade: C—multiple spaces involved by cribriform pattern DCIS with some comedo necrosis. A high-power view of the lesion is shown in F. The cells show that nuclear polymorphism and several mitotic figures are evident.
Figure 3
Figure 3
Histology specimens of the proband’s daughter (age 30), right breast tumor, year 2007. Hematoxylin and Eosin (HE) slides (A,B) illustrate a moderately differentiated (G2) ductal carcinoma composed of trabecular, alveolar structures, and tumor nests. Carcinoma cells revealed an intermediated grade of nuclear polymorphism with mitotic counts up to 8 mitoses/10 HPFs. Intravascular invasion was present (C). The tumor was weakly positive for ER + (D), strongly positive for PR + (E), and negative for HER2 (F).

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